Impact of Off-Hour Admission on In-Hospital Outcomes for Patients With Stroke Receiving Reperfusion Therapy in China.

BACKGROUND: The structure and staffing of hospitals greatly impact patient outcomes, with frequent changes occurring during nights and weekends. This retrospective cohort study assessed the impact of admission timing on in-hospital management and outcomes for patients with stroke receiving reperfusion therapy in China using data from a nationwide registry. METHODS: Data from patients receiving reperfusion therapy were extracted from the Chinese Stroke Center Alliance. Hospital admission time was categorized according to day/evening versus night and weekday versus weekend. Primary outcomes were in-hospital death or discharge against medical advice, hemorrhage transformation, early neurological deterioration, and major adverse cardiovascular events. Logistic regression was performed to compare in-hospital management performance and outcomes based on admission time categories. RESULTS: Overall, 42 381 patients received recombinant tissue-type plasminogen activator (r-tPA) therapy, and 5224 underwent endovascular treatment (EVT). Patients admitted during nighttime had a higher probability of receiving r-tPA therapy within 4.5 hours from onset or undergoing EVT within 6 hours from onset compared with those admitted during day/evening hours (adjusted odds ratio, 1.04 [95% CI, 1.01-1.08]; P=0.021; adjusted odds ratio, 1.72 [95% CI, 1.59-1.86]; P<0.001, respectively). However, no significant difference was observed between weekend and weekday admissions for either treatment. No notable differences were noted between weekends and weekdays or nighttime and daytime periods in door-to-needle time for r-tPA or door-to-puncture time for EVT initiation. Furthermore, weekend or nighttime admission did not have a significant effect on the primary outcomes of r-tPA therapy or EVT. Nevertheless, in patients undergoing EVT, a higher incidence of pneumonia was observed among those admitted at night compared with those admitted during day/evening hours (adjusted odds ratio, 1.22 [95% CI, 1.05-1.42]; P=0.011). CONCLUSIONS: Patients admitted at nighttime were more likely to receive r-tPA therapy or EVT within the time window recommended in the guidelines. However, patients receiving EVT admitted at night had an increased risk of pneumonia.

3D Bioprinted Xanthan Hydrogels with Dual Antioxidant and Chondrogenic Functions for Post-traumatic Cartilage Regeneration.

Intra-articular trauma typically initiates the overgeneration of reactive oxidative species (ROS), leading to post-traumatic osteoarthritis and cartilage degeneration. Xanthan gum (XG), a branched polysaccharide, has shown its potential in many biomedical fields, but some of its inherent properties, including undesirable viscosity and poor mechanical stability, limit its application in 3D printed scaffolds for cartilage regeneration. In this project, we developed 3D bioprinted XG hydrogels by modifying XG with methacrylic (MA) groups for post-traumatic cartilage therapy. Our results demonstrated that the chemical modification optimized the viscoelasticity of the bioink, improved printability, and enhanced the mechanical properties of the resulting scaffolds. The XG hydrogels also exhibit decent ROS scavenging capacities to protect stem cells from oxidative stress. Furthermore, XGMA(H) (5% MA substitution) exhibited superior chondrogenic potential in vitro and promoted cartilage regeneration in vivo. These dual-functional XGMA hydrogels may provide a new opportunity for cartilage tissue engineering.

The Untargeted Metabolomics Reveals Differences in Energy Metabolism in Patients with Different Subtypes of Ischemic Stroke.

AIMS: Ischemic stroke (IS) is the most common subtype of stroke. The risk factors and pathogenesis of IS are complex and varied due to different subtypes. Therefore, we used metabolomics technology to investigate the biomarkers and potential pathophysiological mechanisms of different subtypes of IS. METHODS: We included 126 IS patients and divided them into two groups based on the TOAST classification: large-artery atherosclerosis (LAA) group (n = 87) and small-vessel occlusion (SVO) group (n = 39). Plasma metabolomics analysis was performed using liquid chromatography-high-resolution mass spectrometry (LC-HRMS) to identify metabolic profiles in LAA and SVO subtype IS patients and to determine metabolic differences between patients with the two subtypes of IS. RESULTS: We identified 26 differential metabolites between LAA and SVO subtype IS. A multiple prediction model based on the plasm metabolites had good predictive ability for IS subtyping (AUC = 0.822, accuracy = 77.8%), with 12,13-DHOME being the most important differential metabolite in the model. The differential metabolic pathways between the two subtypes of IS patients included tricarboxylic acid (TCA) cycle, alanine, aspartate and glutamate metabolism, and pyruvate metabolism, mainly focused on energy metabolism. CONCLUSION: 12,13-DHOME emerged as the primary discriminatory metabolite between LAA and SVO subtypes of IS. In LAA subtype IS patients, energy metabolism, encompassing pyruvate metabolism and the TCA cycle, exhibited lower activity levels when compared to patients with the SVO subtype IS. The utilization of targeted metabolomics holds the potential to improve diagnostic accuracy for distinguishing stroke subtypes.

High drug loading hydrophobic cross-linked dextran microspheres as novel drug delivery systems for the treatment of osteoarthritis.

Drug delivery via intra-articular (IA) injection has proved to be effective in osteoarthritis (OA) therapy, limited by the drug efficiency and short retention time of the drug delivery systems (DDSs). Herein, a series of modified cross-linked dextran (Sephadex, S0) was fabricated by respectively grafting with linear alkyl chains, branched alkyl chains or aromatic chain, and acted as DDSs after ibuprofen (Ibu) loading for OA therapy. This DDSs expressed sustained drug release, excellent anti-inflammatory and chondroprotective effects both in IL-1ß induced chondrocytes and OA joints. Specifically, the introduction of a longer hydrophobic chain, particularly an aromatic chain, distinctly improved the hydrophobicity of S0, increased Ibu loading efficiency, and further led to significantly improving OA therapeutic effects. Therefore, hydrophobic microspheres with greatly improved drug loading ratio and prolonged degradation rates show great potential to act as DDSs for OA therapy.

Comparison between healthcare quality in primary stroke centers and comprehensive stroke centers for acute stroke patients: evidence from the Chinese Stroke Center Alliance.

Background: To improve stroke care quality, the guidelines for stroke center construction in China recommended establishing primary stroke centers (PSCs) and comprehensive stroke centers (CSCs). We aimed to compare stroke care quality between the two types of centers. Methods: Data were collected from acute stroke patients admitted to PSCs or CSCs in the China Stroke Center Alliance program. Twenty-one individual guideline-recommended performance measures and two summary measures were compared between the two groups. Multivariable logistic regression models were used to examine the association between stroke center status (CSC vs. PSC) and healthcare quality. Findings: Data from 750,594 stroke patients from 1474 stroke centers (252 CSCs and 1222 PSCs) were analyzed. For many components of healthcare performance in stroke patients, comparable levels of performance were observed between CSCs and PCSs. Nonetheless, CSCs outperformed PSCs in the areas of administering intravenous recombinant tissue plasminogen activator within 4.5 h (aOR = 1.31 [95% CI: 1.07-1.60]), rehabilitation for acute ischaemic stroke (AIS) (aOR = 1.19 [95% CI: 1.01-1.40]), and the provision of hypoglycemic medication and statin therapy upon discharge for AIS (aOR = 1.26 [95% CI: 1.00-1.59] and aOR = 1.28 [95% CI: 1.04-1.59], respectively). More patients with intracerebral haemorrhage and subarachnoid haemorrhage received neurosurgery in CSCs (14.4% vs. 10.6% and 51.0% vs. 33.9%, respectively). Additionally, CSCs had higher in-hospital mortality than PSCs (aOR = 1.33 [95% CI: 1.01-1.73]). Interpretation: Overall PSCs provided equivalent care for many quality measures to CSCs in China with the exception of thrombolysis, rehabilitation access, and medication at discharge for AIS, whereby improvements should be directed. Nevertheless, PSCs have demonstrated lower risk-adjusted in-hospital mortality rates. Funding: The National Key Research and Development Projects of China.

Elevated Chinese visceral adiposity index increases the risk of stroke in Chinese patients with metabolic syndrome.

Introduction: Patients with Metabolic Syndrome (MetS) are considered at high-risk for incident stroke. An indicator of visceral adiposity dysfunction, the Chinese Visceral Adiposity Index (CVAI) is used to evaluate the dysfunction of visceral fat. Given the impact of visceral adiposity dysfunction on elevating cardiovascular hazards, this study aimed to examine the association between CVAI and stroke risk in MetS patients. Method: Between November 2017 and December 2018, a total of 18,974 individuals aged ≥40 underwent standardized in-person clinical interviews in Hunan Province, with 6,732 meeting the criteria for MetS. After the baseline survey was completed, subsequent surveys were conducted biennially. The study was split into two stages performed at baseline and after two years. During the former, receiver-operating characteristic curves were used to assess the accuracy of using baseline CVAI in diagnosing MetS. After two years, we examined the association between CVAI and incident stroke in MetS patients using logistic regression, subgroup analysis, and restricted cubic spline (RCS) analysis. Result: As evidenced by a higher AUC (AUC:0.741), CVAI demonstrated superior diagnostic performance relative to body mass index (AUC:0.631) and waist circumference (AUC:0.627) in diagnosing MetS. After a 2-year follow-up, 72 MetS patients had a stroke event. There was a robust positive correlation between incident stroke and CVAI in patients with MetS. Each 1 SD increase in CVAI was associated with a 1.52-fold higher risk of stroke after adjustment for confounding factors (aOR=1.52, 95%CI: 1.18-1.95). The RCS demonstrated a reduced risk of stroke for MetS patients when the CVAI was below 110.91. However, no significant correlation was detected between CVAI and stroke in non-MetS patients. Conclusion: Our findings recommend CVAI as a superior screening tool for detecting MetS and suggest that reducing CVAI can mitigate the risk of stroke in patients with MetS.

Intracranial hemorrhage management in the multi-omics era.

Intracranial hemorrhage (ICH) is a devastating disorder. Neuroprotective strategies that prevent tissue injury and improve functional outcomes have been identified in multiple animal models of ICH. However, these potential interventions in clinical trials produced generally disappointing results. With progress in omics, studies of omics data, including genomics, transcriptomics, epigenetics, proteomics, metabolomics, and the gut microbiome, may help promote precision medicine. In this review, we focused on introducing the applications of all omics in ICH and shed light on all of the considerable advantages to systematically analyze the necessity and importance of multiple omics technology in ICH.

The association between neutrophil counts and neutrophil-to-lymphocyte ratio and stress hyperglycemia in patients with acute ischemic stroke according to stroke etiology.

Background and purpose: Stress hyperglycemia ratio (SHR), which is used to assess stress hyperglycemia, is associated with the functional outcome of ischemic stroke (IS). IS can induce the inflammatory response. Neutrophil counts and neutrophil-to-lymphocyte ratio (NLR) as good and easily available inflammatory biomarkers, the relationship between neutrophil counts and NLR and SHR were poorly explored in IS. We aimed to systemically and comprehensively explore the correlation between various blood inflammation markers (mainly neutrophil counts and NLR) and SHR. Methods: Data from 487 patients with acute IS(AIS) in Xiangya Hospital were retrospectively reviewed. High/low SHR groups according to the median of SHR (≤1.02 versus >1.02). Binary logistic regression analysis was used to evaluate the correlation between neutrophil counts and NLR and high SHR group. Subgroup analyses were performed in the TOAST classification and functional prognosis. Results: The neutrophil counts and NLR were all clearly associated with SHR levels in different logistic analysis models. In the subgroup analysis of TOAST classification, the higher neutrophil counts and NLR were the independent risk factors for high SHR patients with large-artery atherosclerosis (LAA) (neutrophil: adjusted OR:2.047, 95% CI: 1.355-3.093, P=0.001; NLR: adjusted OR:1.315, 95% CI: 1.129-1.530, P<0.001). The higher neutrophil counts were the independent risk factor for high SHR patients with cardioembolism (CE) (adjusted OR:2.413, 95% CI: 1.081-5.383, P=0.031). ROC analysis showed that neutrophil counts was helpful for differentiating high SHR group with CE and low SHR group with CE (neutrophil: AUC =0.776, P=0.002). However, there were no difference in levels of neutrophil counts and NLR between patients with SVO and without SVO. The higher neutrophil counts and NLR independently associated with high SHR patients with mRS ≤2 at 90 days from symptom onset, (neutrophil: adjusted OR:2.284, 95% CI: 1.525-3.420, P<0.001; NLR: adjusted OR:1.377, 95% CI: 1.164-1.629, P<0.001), but not in patients with mRS >2. Conclusions: This study found that the neutrophil counts and NLR are positively associated with SHR levels in AIS patients. In addition, the correlation between neutrophil counts and NLR and different SHR levels are diverse according to TOAST classification and functional prognosis.

Correction: Carbazate-modified cross-linked dextran microparticles suppress the progression of osteoarthritis by ROS scavenging.

Correction for 'Carbazate-modified cross-linked dextran microparticles suppress the progression of osteoarthritis by ROS scavenging' by Yanfeng Ding, et al., Biomater. Sci., 2021, 9, 6236-6250. https://doi.org/10.1039/D1BM00743B.

Stroke-associated infection in patients with co-morbid diabetes mellitus is associated with in-hospital mortality.

Background and objective: The association between infection and acute ischemic stroke (AIS) with diabetes mellitus (DM) remains unknown. Therefore, this study aimed to explore the effect of infection on AIS with DM. Materials and methods: The data of patients with AIS and DM were extracted from the Chinese Stroke Center Alliance (CSCA) database from August 2015 to July 2019. The association between infections [pneumonia or urinary tract infection (UTI)] and in-hospital mortality was analyzed. Logistic regression models were used to identify the risk factors for in-hospital mortality of patients with infection. Results: In total, 1,77,923 AIS patients with DM were included in the study. The infection rate during hospitalization was 10.5%, and the mortality rate of infected patients was 3.4%. Stroke-associated infection was an independent risk factor for an early poor functional outcome [odds ratio (OR) = 2.26, 95% confidence interval (CI): 1.97-2.34, P < 0.0001] and in-hospital mortality in AIS patients with DM. The in-hospital mortality after infection was associated with age (OR = 1.02, 95% CI: 1.01-1.03, P < 0.0001), male (OR = 1.39, 95% CI: 1.13-1.71, P = 0.0018), reperfusion therapy (OR = 2.00, 95% CI: 1.56-2.56, P < 0.0001), and fasting plasma glucose at admission (OR = 1.05, 95% CI: 1.03-1.08, P < 0.0001). In contrast, antiplatelet drug therapy (OR = 0.63, 95% CI: 0.50-0.78, P < 0.0001) and hospital stay (OR = 0.96, 95% CI: 0.94-0.97, P < 0.0001) were independent protecting factors against in-hospital mortality of patients with infection. Conclusion: Infection is an independent risk factor of in-hospital mortality for patients with AIS and DM, and those patients require strengthening nursing management to prevent infection.

A novel multifunctional anti-PD-L1-CD16a-IL15 induces potent cancer cell killing in PD-L1-positive tumour cells.

Cancer is the most acute disease and the leading cause of patient death worldwide. Both chemotherapy and molecular-based therapies play an important role in curing cancer. However, the median and overall survival of patients is poor. To date, immune therapies have changed the treatment methods for cancer patients. Programmed death ligand 1 (PD-L1, also known as B-H1, CD274) is a well-studied tumor antigen. PD-L1 is overexpressed in colon cancer, lung cancer, and so on and plays a vital role in cancer development. In this study, anti-PD-L1 single-domain antibodies were identified from recombinant human PD-L1 (rhPD-L1)-immunized llamas. Then, we generated a novel multifunctional anti-PD-L1-CD16a-IL15 antibody targeting PD-L1-positive tumor cells. Anti-PD-L1-CD16a-IL15 was constructed by linking the Interleukin-2 (IL-2) signal peptide, anti-PD-L1 single domain antibody (anti-PD-L1-VHH) and anti-cluster of differentiation 16a single domain antibody (anti-CD16a-VHH), and Interleukin-15/Interleukin-15 receptor alpha (IL15/IL-15Rα). This anti-PD-L1-CD16a-IL15 fusion protein can be expressed and purified from HEK-293F cells. In vitro, our data showed that the anti-PD-L1-CD16a-IL15 fusion protein can recruit T cells and drive natural killer cells (NK) with specific killing of PD-L1-overexpressing tumor cells. Furthermore, in the xenograft model, the anti-PD-L1-CD16a-IL15 fusion protein inhibited tumor growth with human peripheral blood mononuclear cells (PBMCs). These data suggested that the anti-PD-L1-CD16a-IL15 fusion protein has a latent function in antitumour activity, with better guidance for future cancer immunotherapy.

In Situ Reduced Graphene Oxide and Polyvinyl Alcohol Nanocomposites With Enhanced Multiple Properties.

The nanocomposites formed by graphene oxide (GO) and carbazate-modified polyvinyl alcohol (PVA-N) were developed to investigate their multiple properties for wide applications. Their physicochemical characterizations confirmed that the in situ reduced GO (rGO) not only decreased the crystallization but also induced the porous structures inside the nanocomposites. Significantly, it revealed that the comprehensive performance of PVA-N2-2%GO consisted of PVA-N2 with the carbazate degree of substitution (DS) of 7% and the weight ratio (wt%) of 2% GO displayed 79% of tensile elongation and tensile strength of 5.96 N/mm2 (MPa) by tensile testing, glass transition temperature (Tg) of 60.8°C and decomposition temperature (Td) of 303.5°C by TGA and DSC, surface contact angle at 89.4 ± 2.1°, and electrical conductivity of 9.95 × 10-11 S/cm. The abovementioned comprehensive performance was enhanced with the increased amount of in situ rGO, contributed by the high DS of the carbazate group in PVA-N and high amount of GO. The rGO by in situ reduction was the main driving force for enhancing the multiple properties inside the nanocomposites.

Association of PI3K-Akt Pathway-Related Gene Polymorphisms with Symptomatic Intracranial Atherosclerotic Stenosis with Hypertension in a Chinese Han Population.

BACKGROUND: PI3K-Akt signaling has been proved to be closely related to atherosclerosis, and hypertension has been shown to be an important risk factor for atherosclerosis. Studies have shown that genetic susceptibility is important in the etiology of symptomatic intracranial atherosclerotic stenosis (sICAS). However, few candidate genes have been identified. In the present study, we explored latent connections between single nucleotide polymorphisms (SNPs) of PI3K-Akt-related genes and sICAS with hypertension in Han Chinese subjects. METHODS: Eight genes related to the PI3K-Akt pathway in 400 patients with sICAS and 1007 healthy controls of Han nationality were sequenced, and further subgroup analysis stratified by the presence of hypertension was performed. The χ2 test and multiple logistic regression in dominant, recessive, and additive models were used to evaluate the association between the SNPs and the risk of sICAS with hypertension. When linkage disequilibrium was found in different loci of the same gene, tagSNP represents the SNP in the haplotype block. RESULTS: We found 4 common variants of 1 candidate gene differently distributed between those with sICAS with and without hypertension. Among these 4 common variations, INSR (insulin receptor) rs3745551 was significantly related to the risk of sICAS with hypertension after multiple regression analysis, with the T allele more prevalent in sICAS with hypertension. CONCLUSIONS: The variant of the INSR rs3745551 loci might be crucial to the pathogenesis of sICAS with hypertension in Chinese Han populations. Furthermore, the C allele at this locus might be a potentially harmful variant in sICAS with hypertension.

Alterations in the gut microbiome with hemorrhagic transformation in experimental stroke.

OBJECTIVE: Hemorrhagic transformation (HT) is a life-threatening complication of stroke. Whether changes in gut microbial composition underlie the development of HT remains unknown. This study aimed to investigate whether the gut microbiota is altered in HT rats and examine the association between these changes and inflammatory responses. METHODS: HT was successfully established in rats injected with 50% glucose (6 ml/Kg, i.p.) 15 min before middle cerebral artery occlusion (MCAO, 90 min occlusion) with reperfusion. After 5 days, rats were euthanized, and their brains used to estimate infarct volume. The inflammatory factors, the analysis of gut microbiota, and short-chain fatty acids (SCFA) were assessed. RESULTS: In contrast with non-HT rats, gut microbiota sequencing showed an elevation in the relative abundance of Proteobacteria and Actinobacteria in HT rats. Total SCFAs, especially butyrate and valeric acid, were significantly lower in the cecal contents of HT rats than in those of non-HT rats. Hyperglycemia-induced HT exacerbation was not observed when rats were treated with antibiotics, suggesting that altered microbiota play a critical role in hyperglycemic HT pathogenesis. Furthermore, rats whose gut was colonized with HT rat microbiota showed increased susceptibility to HT. CONCLUSION: This study provides important information about the gut microbiota profiles and SCFA levels of MCAO rats with HT or non-HT. The susceptibility to HT in MCAO rats is associated with inflammation and gut microbiota modulation.

Association of Plasma Metabolic Biomarker Sphingosine-1-Phosphate With Cerebral Collateral Circulation in Acute Ischemic Stroke.

Background: The contribution of metabolic profile to the cerebral collateral circulation in acute ischemic stroke (AIS) has not been fully outlined. In this study, we conducted a metabolomic study to assess the relationship between the metabolic biomarkers and the collateral status of AIS. Methods: A two-stage study was conducted from September 2019 to June 2021 in our hospital. There were 96 subjects including 66 patients with AIS and 30 healthy controls in the discovery stage and 80 subjects including 53 patients with AIS and 27 healthy controls in the validation stage. Collateral circulation was assessed by the Tan score based on computed tomographic angiography (CTA). Liquid chromatography-tandem mass spectrometry was used to identify differential metabolic markers. Then, an ELISA was employed to detect the plasma levels of sphingosine-1-phosphate (S1P). Results:There were 114 differential metabolites between patients with AIS and control groups and 37 differential metabolites between good collateral circulation (GCC) and poor collateral circulation (PCC) groups. The pathway enrichment analysis revealed that arginine biosynthesis was the only statistically significant pathway between AIS and control groups and sphingolipid metabolism was the only statistically significant pathway between GCC and PCC groups. The differential metabolites sphinganine-1-phosphate (SA1P) and S1P belong to the sphingolipid metabolism. In the discovery stage, when the GCC group was compared with the PCC group, the receiver operating characteristic (ROC) analysis showed that plasma SA1P relative levels demonstrated an area under the curve (AUC) of 0.719 (95% CI: 0.582-0.834), and S1P levels demonstrated an AUC of 0.701 (95% CI: 0.567-0.819). In addition, both plasma SA1P and S1P relative levels showed significant negative correlations with the 90-day modified Rankin Scale (mRS) score. In the validation sample, higher plasma S1P levels were independent predictors of GCC (p = 0.014), and plasma S1P levels demonstrated an AUC of 0.738 (95% CI: 0.599-0.849) to differentiate patients with GCC from patients with PCC. In addition, plasma S1P levels also showed significant negative correlations with the 90-day mRS score. Conclusion: We first illustrated the association between plasma metabolic profiles and cerebral collateral circulation in patients with AIS. Plasma S1P levels might be a potential diagnostic biomarker for predicting collateral circulation status in patients with AIS.

Serum Bilirubin Levels and Extent of Symptomatic Intracranial Atherosclerotic Stenosis in Acute Ischemic Stroke: A Cross-Sectional Study.

Background: Bilirubin plays a paradoxical role in the pathological mechanism of stroke. To date, few clinical studies have investigated the effect of serum bilirubin on symptomatic intracranial atherosclerotic stenosis (sICAS). This study aims to evaluate the connection between serum bilirubin and sICAS. Methods: From September 2015 to May 2020, 1,156 sICAS patients without hepatobiliary diseases admitted to our hospital were included. Patients were distributed into none-mild (0-49%), moderate (50-69%) and severe-occlusion sICAS groups (70-100%) by the degree of artery stenosis. Moderate and severe-occlusion sICAS patients were classified into three groups by the number of stenotic arteries (single-, two- and multiple-vessel stenosis). The relationship between serum bilirubin levels and sICAS was analyzed by logistic regression analysis. Results: In univariable analyses, sICAS patients with severe and multiple atherosclerotic stenoses had lower levels of total bilirubin (Tbil), direct bilirubin (Dbil), and indirect bilirubin (Ibil). In multinomial logistic regression analyses, when compared with the highest tertile of bilirubin, lower levels of Tbil, Dbil, and Ibil showed higher risks of severe-occlusion sICAS (95% CI: 2.018-6.075 in tertile 1 for Tbil; 2.380-7.410 in tertile 1 for Dbil; 1.758-5.641 in tertile 1 for Ibil). Moreover, the logistic regression analyses showed that lower levels of Tbil, Dbil, and Ibil were related to multiple (≥3) atherosclerotic stenoses (95% CI: 2.365-5.298 in tertile 1 and 2.312-5.208 in tertile 2 for Tbil; 1.743-3.835 in tertile 1 and 1.416-3.144 in tertile 2 for Dbil; 2.361-5.345 in tertile 1 and 1.604-3.545 in tertile 2 for Ibil) when compared with tertile 3. Conclusions: Our findings suggest that lower bilirubin levels may indicate severe and multiple intracranial atherosclerotic stenoses.

Carbazate-modified cross-linked dextran microparticles suppress the progression of osteoarthritis by ROS scavenging.

A series of modified polysaccharide microparticles have been fabricated and their potential application for scavenging reactive oxygen species (ROS) and their derivatives to achieve osteoarthritis (OA) treatment has been explored. These microparticles were cross-linked dextran (Sephadex) with different carbazate substitution ratios determined by the TNBS assay and elemental analysis. It has been demonstrated that they could effectively scavenge carbonylated proteins and ROS including hydroxyl radicals (˙OH), superoxide anions (˙O2-) and H2O2 and their derivatives with high efficiency, improve the viability of H2O2-treated chondrocytes by reducing their ROS levels, as well as lower their inflammatory factors. The above ability of antioxidation and inflammation resistance improved with the increase of carbazate substitution ratio. Significantly, this work provided the proof that modified Sephadex successfully alleviated the deterioration of cartilage and the progression of OA in vivo. The proposed microparticles showed a very promising capability for reducing ROS levels and further treating OA.

Gut-Derived Metabolite Phenylacetylglutamine and White Matter Hyperintensities in Patients With Acute Ischemic Stroke.

Background: White matter hyperintensity (WMH) burden is associated with a higher risk of ischemic stroke. Phenylacetylglutamine (PAGln) is a gut microbiota-derived metabolite that may induce cardiovascular events by activating platelets and increasing the risk of thrombosis. The relationship between plasma PAGln and WMH burden in patients with ischemic stroke is unknown. This study was designed to investigate the association between plasma PAGln and WMH burden in patients with acute ischemic stroke. Methods: A total of 595 patients with acute ischemic stroke were enrolled in this study within 14 days of symptom onset. The burden of WMH was evaluated using the Fazekas scale based on the fluid-attenuated inversion recovery sequence. The severity of overall WMH was defined as none-mild WMH (total Fazekas score 0-2) or moderate-severe WMH (total Fazekas score 3-6). Based on the severity of periventricular WMH (P-WMH) and deep WMH (D-WMH), patients were categorized into either a none-mild (Fazekas score 0-1) group or a moderate-severe (Fazekas score 2-3) group. Plasma PAGln levels were quantified using liquid chromatography-mass spectrometry. Results: We found that patients with moderate-severe overall WMH showed higher plasma PAGln levels than patients with none-mild overall WMH, and similar results were found in the analyses according to P-WMH and D-WMH. The logistic regression analysis showed that the fourth PAGln quartile was independently associated with moderate-severe overall WMH (adjusted 95% CI 1.134-4.018) and P-WMH (adjusted 95% CI 1.174-4.226). Conclusion: These findings suggest that higher plasma PAGln levels are associated with moderate-severe overall WMH and P-WMH in patients with acute ischemic stroke.

Neutrophil-to-Lymphocyte Ratio as a Predictive Biomarker for Stroke Severity and Short-Term Prognosis in Acute Ischemic Stroke With Intracranial Atherosclerotic Stenosis.

Background: Neutrophil-to-lymphocyte ratio (NLR) is an indicator of poor prognosis in acute ischemic stroke (AIS), but associations between NLR with stroke severity and prognosis of intracranial atherosclerotic stenosis (ICAS)-related ischemic events have not been well-elucidated; therefore, we aimed to evaluate whether admission NLR levels correlate with the early stroke severity and short-term functional prognosis in patients with symptomatic intracranial atherosclerotic stenosis (sICAS). Methods: This retrospective study enrolled 899 consecutive patients with AIS attributed to ICAS at Xiangya Hospital stroke center between May 2016 and September 2020. The initial stroke severity was rated by the admission National Institutes of Health Stroke Scale (NIHSS) scores, and the short-term prognosis was evaluated using the 14-day modified Rankin Scale (mRS) scores after stroke onset. A severe stroke was defined as NIHSS >8; an unfavorable functional outcome was defined as mRS scores of 3-6. Admission NLR was determined based on circulating neutrophil and lymphocyte counts. Results: The median admission NLR of all patients was 2.80 [interquartile range (IQR), 2.00-4.00]. In univariate analysis, admission NLR was significantly elevated in patients with severe stroke and poor short-term prognosis. After multivariate adjustment, admission NLR levels were significantly correlated with severe stroke [odds ratio (OR), 1.132; 95% confidence interval (95% CI), 1.038-1.234; P = 0.005] and unfavorable short-term prognosis (OR, 1.102; 95% CI, 1.017-1.195; P = 0.018) in Model 1. In Model 2, the highest NLR tertile (≥3.533) remained an independent predictor of severe stroke (OR, 2.736; 95% CI, 1.590-4.708; P < 0.001) and unfavorable functional outcome (OR, 2.165; 95% CI, 1.416-3.311; P < 0.001) compared with the lowest NLR tertile (<2.231). The receiver operating characteristic (ROC) curves showed the predictability of NLR regarding the stroke severity [area under the curve (AUC), 0.659; 95% CI, 0.615-0.703; P < 0.001] and short-term prognosis (AUC, 0.613; 95% CI, 0.575-0.650; P < 0.001). The nomograms were constructed to create the predictive models of the severity and short-term outcome of sICAS. Conclusions: Elevated admission NLR levels were independently associated with the initial stroke severity and could be an early predictor of severity and poor short-term prognosis in AIS patients with ICAS, which might help us identify a target group timely for preventive therapies.